Pre-filled syringe

ABSTRACT

A pre-filled syringe comprising a glass barrel ( 1 ), a sealing member ( 5 ) fitted in a medical liquid discharge port ( 11 ) of the barrel ( 1 ), a tip member ( 2 ) mounted around the sealing member ( 5 ) on the medical liquid discharge port ( 11 ) of the barrel ( 1 ), a closing member ( 4 ), a cap member ( 3 ), and a holding member ( 6 ); the sealing member ( 5 ) having a through-hole ( 51 ) formed in the axial direction; the tip member ( 2 ) including a skirt ( 24 ) provided with an engagement pawl ( 25 ) on the inner wall of a lower end thereof, a top wall ( 23 ), a needle mounting portion ( 21 ), and a medical liquid deriving portion ( 22 ), and being provided with a medical liquid passage ( 28 ); the closing member ( 4 ) being inserted into the medical liquid passage ( 28 ) and the through-hole ( 51 ) to close the through-hole ( 51 ) and so prevent oxygen contamination and deterioration of the medical liquid.

REFERENCE TO RELATED APPLICATIONS

This application is a 35 U.S.C. 371 National Stage Application ofInternational Patent Application No. PCT/GB01/01433, filed Mar. 28,2001.

The present invention relates to a syringe which is filled in advancewith a liquid to be injected. More particularly, the invention relatesto an improvement in a pre-filled syringe which has a barrel of glassand which can select the position and shape of a needle mounting portionarbitrarily.

In the manufacture of the pre-filled syringe of the prior art using aglass barrel, the needle mounting portion is formed into a hollow nozzleconverged, as a so-called “luer tip”, into a taper shape. This luer tipmay be formed by (i) a method of working a glass pipe; (ii) a method offixing the luer tip member on the mouth of the barrel (having the shapeof a vial mouth) through packing by a caulking member of aluminum; and(iii) a method of press-fitting a rubber plug holding member with theluer tip of hard plastic of the mouth barrel.

In the method (i) comprising heating, melting and embossing the glasspipe, the sizing accuracy is poor, so that the portion to be fitted inpartnership (such as the hub of a needle or a female luer connector) hasto be polished for a higher sizing accuracy by means of a grindingstone. Furthermore, the polishing work is difficult to automate andrequires checking of all the individual parts, so that the method isextremely low in productivity and high in cost.

In the method (ii), on the other hand, the caulking member is made fromaluminium. When the luer tip member is wound around the mouth of barrel,therefore, fine powder of aluminium may be produced to contaminate thesterile room or to mix as a foreign substance into a medical liquidcontained in the syringe. Another defect is that the aluminium memberhas to be separated and scrapped. Like the method (i) the method (iii)comprises a polishing treatment because it is necessary to have accuratesizing in the external diameter of the mouth of the barrel. Since theluer tip member of hard plastic (such as polycarbonate) is forciblypress-fitted problems are frequently encountered by cracking in thepress-fitted portion of the rubber plug holder. In the case of a glassbarrel, the tip is positioned on the centreline of the glass barrel. Ina syringe having a capacity of 20 milliliters or more, generally, thereis problem that the needle so positioned is hard to insert into a(human) body.

In order to solve the above-specified problems, a pre-filled syringe wasproposed in Japanese Patent Application Laid-Open Nos. (a) Hei-07-80065and (b) Hei-07-313596 (European Patent Application No. 685237, U.S. Pat.No. 5,624,405).

The former pre-filled syringe (a) comprises a barrel of glass; a tipmember fitted liquid-tightly on a medical liquid discharge port at adistal end of the barrel; a sealing member for sealing the tip memberand the medical liquid discharge port liquid-tightly: a cap-shapedmember for caulking and fixing the sealing member on the medical liquiddischarge port; and a sealing member for sealing a needle mountingportion of a distal end of the tip member, and is characterized in thatthe inside is filled with a medical liquid, and in that the proximal endopening of the barrel is closed by a plunger inserted liquid-tightlythereinto.

In this pre-filled syringe, however, the sealing member mounted on theneedle portion of the tip member can be arbitrarily mounted/demounted toraise a problem that the medical liquid contained therein may betampered with or contaminated.

The latter pre-filled syringe (b) comprises a barrel made of glass andhaving at the distal end thereof a medical liquid discharge port formedin the shape of a vial mouth; a sealing member fitted in the medicalliquid discharge port of the barrel and having a through-hole in theaxial direction; a tip member including a skirt provided with anengagement pawl on a lower end inner wall thereof, a top wall, a needlemounting portion and a medical liquid deriving portion and forming amedical liquid passage through the medical liquid deriving portion, thetop wall and the needle mounting portion; a sealing member for sealingthe needle mounting portion of the tip member; and a holding member formounting and fixing the tip member on the medical discharge port of thebarrel, and is characterized in that the tip member is mountedliquid-tightly on the medical liquid discharge port by mounting theholding member around the tip member and sliding downward along theskirt thereof.

However, the latter pre-filled syringe has a portion where the medicalliquid and the tip member (of a thermoplastic resin) are in contact witheach other, and a gas (e.g. oxygen) outside of the syringe mayinfiltrate from that portion into the medical liquid thereby raising theproblem that the medical liquid deteriorates in potency, and maygenerate degradation by-products over time, if unstable in the presenceof oxygen.

The present invention has however been conceived in view of thebackground thus far described and has an object to solve the abovespecified problems by improving, in particular, the pre-filled syringeof Japanese Patent Application Laid-Open No. Hei-07-313596.

We have keenly made investigations to solve those problems and foundthat the tampering and deterioration of a medical liquid can besimultaneously prevented if a closing member integrated with a capmember is inserted into a medical liquid passage of a tip member and athrough-hole of a sealing member thereby to close the through-hole,

According to the invention, more specifically, there is provided apre-filled syringe comprising: a barrel made of glass and having at adistal end thereof a medical liquid discharge port formed into the shapeof a vial mouth; a sealing member fitted in the medical liquid dischargeport of the barrel and having a through-hole in the axial direction; atip member including a skirt provided with an engagement pawl on a lowerend inner wall thereof, a top wall, a needle mounting portion and amedical liquid deriving portion and forming a medical liquid passagethrough the medical liquid deriving portion, the top wall and the needlemounting portion, and so mounted around the sealing member on themedical liquid discharge port of the barrel as to slide along the outerwall of the medical liquid discharge port; a cap member mounted aroundthe tip member; a closing member made integral with the cap member andinserted into the medical liquid passage of the tip member and thethrough-hole of the sealing member for closing the through-hole; and aholding member for mounting and fixing the tip member on the medicalliquid discharge port of the barrel, wherein the tip member is mountedliquid-tightly on the medical liquid discharge port by mounting theholding member around the tip member and sliding downward along theskirt of the tip member to bring the enagement pawl of the tip memberinto engagement with the medical liquid discharge port of the syringe.

Here, the sealing member may be a rubber plug having an annular rib onthe top wall thereof so as to regain the liquid-tightnesss of themedical liquid passage. On the other hand, it is preferable that the tipmember is provided on the skirt thereof with an axial slit so as tofacilitate an inward flexure and at the outer wall of a lower endportion thereof with retaining means for engaging with the holdingmember. It is preferable that the needle mounting portion includes aninner side tip and outer side female joint means which areconcentrically protruded on the outer side of the top wall of the tipmember. On the other hand, the needle mounting portion may be positionedeccentric from the axis of the tip member. The holding member may beprovided at the lower end inner wall thereof with a skirt having anengagement pawl for engaging with the retaining means of the tip member,and a top wall having a hole. It is preferable that the cap memberincludes concentric inner and outer caps which are mounted around thetip of the needle mounting portion and the female joint means,respectively.

In the case of the cap member including the inner cap and the outer cap,the holding member is temporarily assembled with the upper end portionof the skirt of the outer cap, so that the engagement pawl of the tipmember can be brought into engagement with the medical liquid dischargeport of the syringe by sliding the holding member downward along theouter cap and the skirt of the tip member.

The pre-filled syringe of the present invention may have tamperingprevention. Therefore, for example, the outer cap may be provided with aflange at a skirt lower end portion and the flange removably heldbetween the top wall of the holding member and top wall of the tipmember. In this case, the flange may be provided with a fragile portionand the flange may be broken at the fragile portion when the cap memberis removed. On the other hand, the flange may be formed thin and theflange may be transformed and come off between the top wall of theholding member and the top wall of the tip member when the cap member isremoved. The flange may be provided a fanwise slit. On the other hand,it is preferable that the outer cap is covered with a cylindrical covercap which connects with the top wall of the holding member through thefragile portion, and the cylindrical cover cap can be broken from thetop wall of the holding member for the tampering prevention. In thiscase, the cap member may be removed with the cylindrical cover cap.

The invention is now illustrated, but not limited, by reference to thefollowing embodiments of the invention which are described withreference to the accompanying drawings.

FIG. 1 is a longitudinal section view showing one embodiment of theinvention;

FIG. 2 is an enlarged section view of a tip member shown in FIG. 1;

FIG. 3 is an enlarged top plan view of an integral structure of a capmember and a closing member shown in FIG. 1;

FIG. 4 is a section view along line X—X of FIG. 3;

FIGS. 5 and 6 are enlarged section views of a sealing member and aholding member,

FIG. 7 is a longitudinal section view showing another embodiment of thesealing member.

FIGS. 8 to 10 are longitudinal section views showing other embodimentsof the invention;

FIG. 11 is a top plan view of a cap member shown in FIG. 8;

FIGS. 12 to 14 are top plan views of the embodiments of the cap membershown in FIG. 9;

FIG. 15 is a top plan view of a cap member shown in FIG. 10;

FIG. 16 is a top plan view of the holding member shown in FIG. 10;

FIG. 17 is a longitudinal section view of the holding member shown FIG.10.

FIG. 18 is an explanatory view showing relations among the tip member,the cap member, the closing member and the holding member shown in FIG.1 and shows a state before they are mounted on a medical liquiddischarge port of a barrel. On the other hand,

FIGS. 19 to 22 are explanatory views of a method of attaching thesealing member, the tip member, the cap member, the closing member andthe holding member to the medical liquid discharge port of the barrel.

Referring now to FIG. 1, there is shown a pre-filled syringe accordingto the present invention. The pre-filled syringe comprises a barrel (1)made of glass, a sealing member (5) fitted in a medical liquid dischargeport (11) of the barrel (1), a tip member (2) mounted around the sealingmember (5) on the medical liquid discharge port (11) of the barrel (1),a closing member (4), a cap member (3), and a holding member (6). Thesealing member (5) has a through-hole (51) formed in the axialdirection. The tip member (2) includes a skirt (24) provided with anengagement pawl or projection (25) on the inner wall of a lower endthereof, a top wall (23), a needle mounting portion (21), and a medicalliquid deriving portion (22), and is provided with a medical liquidpassage (28), as shown in FIG. 2. The closing member (4) is insertedinto the medical liquid passage (28) and the through-hole (51) to closethe through-hole (51). The tip member (2) can be mounted liquid-tight onthe medical liquid discharge port (11) by mounting the holding member(6) around the tip member (2) and by sliding the holding member (6)downward along the skirt (24) of the tip member (2) to bring theengagement pawl (25) of the tip member (2) into engagement with themedical liquid discharge port (11).

The barrel (1) is a container made of glass and having two open ends,and the medical liquid discharge port (11) at a distal end thereof isformed into a shape like that of a vial mouth and a side wall of themedical liquid discharge port (11) is annularly bulged at a distal endthereof, and is formed into a flange (12) at a proximal end thereof. Thebarrel (1) is filled with a (not-shown) medical liquid and is closed ata proximal end opening thereof with a gasket (7) inserted liquid-tightlythereinto. This gasket (7) is made slidable in the bore of the barrel,and a plunger (8) is (or can be) coupled to the proximal end thereof.This gasket (7) is ordinarily made of a rubbery elastic material such asnatural rubber or synthetic rubber (e.g. butyl rubber or isoprenerubber), or a thermoplastic elastomer.

In the medical liquid discharge port (11) at a distal end of the barrel(1), there is mounted a rubber plug (5) as the sealing member. Thisrubber plug (5) is made of a material similar to that of the gasket (7)and is provided at a top wall thereof with a flange (52) for sealing adistal end face of the medical liquid discharge port (11) and in theaxial direction with the through-hole (51) as shown in FIG. 5. Into thisthrough-hole (51), there is inserted liquid-tightly the closing member(4), as will be described hereinafter. The through-hole (51) is radiallyextended on a top wall side thereof to form a recess (53), in which themedical liquid deriving porition (22) of the later-described tip member(2) is inserted liquid-tightly. The rubber plug (5) may be provided withan annular rib (54), as shown in FIG. 7, so as to retain theliquid-tightness of the medical liquid passage of the later describedtip member (2).

The tip member (2) is mounted over the rubber plug (5) on the medicalliquid discharge port (11) of the barrel (1) to push the flange (52) ofthe rubber plug (5) on the medical liquid discharge port (11).Generally, the tip member (2) is made of a flexible resin such aspolypropylene, polyethylene, cyclic olefin copolymer or an ABS resin.Referring now to FIG. 2, the tip member (2) includes the top wall (23),the skirt (24), the needle mounting portion (21) protruded outward ofthe top wall (23), and the medical liquid deriving portion (22)protruded outward. The tip member (2) can slide along the outer wall ofthe medical liquid discharge port (11). The skirt (24) is gentlydiverged downward in a taper shape and is provided at a lower end innerwall and at a lower end outer wall thereof, respectively, with theengagement pawl (25) for engaging with the medical liquid discharge port(11) and retaining means (26) for engaging with an engagement pawl orprojection (64) of the later-described holding member (6). The skirt(24) is preferably provided in an axial direction thereof with one ormore slits (27) so that it can warp outward. The preferable member ofthe slits (27) is three or four. The medical liquid passge (28) isformed through the medical liquid deriving portion (22), the top wall(23) and the needle mounting portion (21) so that the medical liquid, ascontained in the barrel (1), is ejected by way of that medical liquidpassage (28). The needle mounting portion (21) is a piped protuberance(or tip (211)) provided with the medical liquid passage (28) and isordinarily converged toward the distal end in a taper shape. The needlemounting portion (21) is preferred to have the so-called “luer locktype” composed of the concentric inner tip (211) and outer female jointmeans (212), as shown in FIG. 2. In this case, the medical liquidpassage (28) is closed by an inner cap (32) of the later-described capmember (3) to be mounted around the tip (211). In the case of a barrelhaving a large capacity, the needle mounting portion (21) and themedical liquid deriving porition (22) may be formed eccentric withrespect to the axis of the tip member (2) so that the needle may beeasily inserted into the skin of a patient.

The engagement pawl (25) on the lower end inner wall of the skirt (24)comes into engagement with the medical liquid discharge port (11) whenthe tip member (2) slides along the outer wall of the medical liquiddischarge port (11) of the barrel (1) and reaches a slide end point. Onthe other hand, the retaining means (26) at the lower end outer wall ofthe skirt (24) comes into engagement with the engagement pawl (64) ofthe holding member (6) when the holding member (6) slides along theskirt (24) of the tip member (2) and reaches a slide end point.

If necessary, the top wall (23) may be provided with an extractingwindow (29) at moulding time, and the skirt (24) may also be provided atan upper portion thereof with a (not shown) shallow engagement groovefor removably engaging with the engagement pawl (64) of the holdingmember (6), so that the holding member (6) may be placed in the statemounted on the tip member (2). If, in this case, the holding member (6)and the cap member (3) are mounted on the tip member (2), the tip member(2) and the holding member (6) can be mounted on the medical liquiddischarge port (11) of the barrel (1) by a single action.

The cap member (3) is fitted on the needle mounting portion (21) of thetip member (2), and the closing member (4) is integrally mounted on theinner side of the top wall of the cap member (3) either by the integralmoulding (or insert moulding) method or by the jointing method. The capmember (3) is generally made of a flexible resin such as polypropylene,polyethylene, cyclic olefin copolymer or an ABS resin, and the closingmember (4) to be integrated with the former is generally made ofstainless steel or glass having excellent gas barrier properties. Whenthe needle mounting portion (21) of the tip member (2) is of the luerlock type, the cap member (3) adopted is composed of an outer cap (31)and the inner cap (32) which are made concentric, as shown in FIGS. 3and 4. In the cap member (3) of this type, the closing member (4) ismounted on the inner cap (32). The outer cap (31) is provided at a topwall thereof with an annular ridge (33) so that the upper end portion ofthe holding member (6) is temporarily fixed adjacent to the annularridge (33) when the tip member (2), the holding member (6) and the capmember (3) are temporarily assembled, as shown in FIG. 18. The closingmember (4) has a slightly larger external diameter than that of thethrough-hole (51) of the sealing member (5) so that it is inserted, whenthe cap member (3) is assembled with the medical liquid discharge port(11) of the barrel (1), into the through-hole (51) of the sealing member(5) to shield the medical liquid contained in the barrel (1) from theatmosphere.

On the tip member (2) fitting the cap member (3) on a needle mountingportion (21), here is mounted the holding member (6) over the cap member(3). The holding member (6) is made of a synthetic resin similar to thatof the tip member (2) and is composed of the top wall (61) having a hole(62) and a skirt (63), as shown in FIG. 6. When the holding member (6)slides downward along the outer wall of the skirt (24) of the tip member(2), the skirt (24) is pushed to warp inward to bring an engagement pawl(25) into engagement with the medical liquid discharge port (11) of thebarrel (1). On the other hand, an engagement pawl (64) which is formedon the lower end inner wall of the holding member (6) comes intoengagement with the retaining means (e.g. undercut) (26) formed in thelower end outer wall of the tip member (2), at a position where theinner side of the top wall (61) of the holding member (6) abuts againstthe top wall (23) of the tip member (2). The holding member (6) istemporarily mounted, when it is temporarily assembled with the tipmember (2) and the cap member (3), as shown in FIG. 18, an upper endportion thereof at the position adjacent to the annular ridge (33) ofthe cap member (3), as described hereinbefore, and at the engagementpawl (64) of a lower end portion thereof with the top wall (23) of thetip member (2). At the temporarily assembling time, therefore, theholding member (6) can be temporarily assembed with the cap member (3)and the tip member (2) to expect an effect that the number of partfeeders can be reduced at the manufacturing time, for example.

The pre-filled syringe of the present invention may have the tamperingprevention as shown in FIG. 8 to 10.

The outer cap (31) is provided with a flange (311) at a skirt lower endportion and the flange (311) removably held between the top wall (61) ofthe holding member (6) and the top wall (23) of the tip member (2), asshown in FIG. 8. The flange (311) is provided with a fragile portion(312) shown in FIG. 11 for example and the flange (311) is broken at thefragile portion (312) when the cap member (3) is removed.

FIG. 9 shows the outer cap (31) in which the flange (313) is formed thinfor giving flexibility in the same composition as FIG. 8. The flange(313) is transformed and comes off between the top wall (61) of theholding member (6) and the top wall (23) of the tip member (2) when thecap member (3) is removed. Here, the flange (313) may be formed as shownin FIG. 12. In this case, the intervals of the top wall (61) of theholding member (6) and the top wall (23) of the tip member (2) are madea little wider than the thickness of the flange (313) for transformingof the flange (313). In the case when the intervals of the top wall (61)of the holding member (6) and the top wall (23) of the tip member aremade of similar thickness to the flange (313), the flange (313) may beprovided with a fanwise slit (314) as shown in FIG. 13, and in anextreme case, the flange (313) may be formed as shown in FIG. 14.

FIG. 10 shows that the outer cap (31) is covered with a cylindricalcover cap (65) which connects with the top wall (61) of the holdingmember (6) through the fragile porition (651) as shown in FIG. 16 forexample, and the cylindrical cover cap (65) can be broken from the topwall (61) of the holding member (6) for tamperingprevention/tamper-proof evidence. In this case, the cap member (3) andthe holding member (6) are formed respectively such as FIG. 15, FIG. 16and FIG. 17, and the cap member (3) and the cylindrical cover cap (65)may be removed from the tip member (2) together. In this composition,the cap member (3) is connected with tip (211) by male joint means (35)which are provided on miner cap (32) as shown in FIG. 15. The holdingmember (6) is turned in the direction where the combination of the innercap (32) and the top (211) is cancelled, the cylindrical cover cap (65)is broken first from the top wall (61) in the fragile portion (651).After this, the longitudinal ribs (652) which are provided at theoutside wall of the outer cap (31) of the cap member (3) as shown inFIG. 17 are engaged with the longitudinal ribs (34) which are providedat the inside wall of the cylindrical cap (65) of the holding member (6)as shown in FIG. 15, the cap member (3) is rotated with the cylindricalcover cap (65) and the cap member (3) is removed from the tip member(2).

The assembly of the pre-filled syringe of the invention is now describedwith reference to FIGS. 19 to 22.

FIG. 18 shows the state (or the temporary assembly of the tip member andso on) in which the integral structure of the cap member (3) and theclosing member (4) are mounted on the needle mounting portion (21) ofthe tip member (2) after the holding member (6) was lightly mountedaround the tip member (2).

First of all, there is prepared a temporary assembly A of the barrel(1), the sealing member (5), the tip member and so on, as shown in FIG.19. The sealing member (5) is inserted into the medical liquid dischargeport (11) of the barrel (1), as shown in FIG. 20. After this, thetemporary assembly A of the tip member and so on is applied to themedical liquid port (11) and is pushed downward. Then, the tip member(2) is moved downward along the medical liquid discharge port (11) untilit is stopped at a position, as shown in FIG. 21. At this time, the capmember (3) and the closing member (4) are moved downward together withthe tip member (2) so that the closing member (4) is insertedliquid-tightly into the through-hole (51) of the sealing member (5).When the downward movement of the tip member (2) stops, moreover, theholding member (6) slides along the outer wall of the skirt (24) of thetip member (2) to deform the skirt (24) inward thereby to bring anengagement pawl (25) into firm engagement with the medical liquiddischarge port (11). The movement of the holding member (6) stops at theposition where a top wall (61) abuts against the top wall (23) of thetip member (2), so that an engagement pawl is firmly fixed on themedical liquid discharge port (11) (as shown in FIG. 22) while engagingwith the retaining means (26) of tip member (2).

As is apparent from the above description, the pre-filled syringe of theinvention is constructed such that the through-hole of the sealingmember is closed by the closing member having high gas barrierproperties. This construction makes it possible to improve the sealingproperties far better than those of the prior art and to apply thepre-filled syringe even to medical agents unstable to gases such asoxygen.

Also provided by the invention is a pre-filled syringe substantially asdescribed herein and with reference to the Figures. Also provided asfeature of the invention is a method of preventing contamination anddeterioration of a medical liquid by use of a pre-filled syringe of theinvention.

BRIEF DESCRIPTION OF THE DRAWINGS/FIGURES

[FIG. 1] A lontitudinal section view showing one embodiment of theinvention.

[FIG. 2] An enlarged section view of a tip member shown in FIG. 1.

[FIG. 3] An enlarged top plan view of an integral structure of a capmember and a closing member shown in FIG. 1.

[FIG. 4] A section view along line X—X of FIG. 3.

[FIG. 5] An enlarged section view of a sealing member shown in FIG. 1.

[FIG. 6] An enlarged section view of a holding member shown in FIG. 1.

[FIG. 7] A longitudinal section view showing another embodiment of thesealing member.

[FIG. 8] A longitudinal section view showing another embodiment of thepresent invention.

[FIG. 9] A longitudinal section view showing another embodiment of thepresent invention.

[FIG. 10] A longitudinal section view showing another embodiment of thepresent invention.

[FIG. 11] A top plan view of a cap member shown in FIG. 8.

[FIG. 12] A top plan view of the embodiment of the cap member shown inFIG. 9.

[FIG. 13] A top plan view of the embodiment of the cap member shown inFIG. 9.

[FIG. 14] A top plan view of the embodiment of the cap member shown inFIG. 9.

[FIG. 15] A top plan view of a cap member shown in FIG. 10.

[FIG. 16] A top plan view of the holding member shown in FIG. 10.

[FIG. 17] A longitudinal section view of the holding member shown FIG.10.

[FIG. 18] An explanatory view showing the relations among the tipmember, the cap member, the closing member and the holding member shownin FIG. 1, and showing a state before they are mounted on a medicalliquid discharge port of a barrel.

[FIGS. 19–22] An explanatory view of a method for mounting the sealingmember, the tip member, the cap member, the closing member and theholding member on the medical liquid discharge port of the barrel.

Key to Figures 1 barrel 11 medical liquid discharge port 12 flange 2 tipmember 21 needle mounting portion 211 tip 212 female joint means 22medical liquid deriving means 23 top wall 24 skirt 25 engagement pawl 26retaining means 27 slit 28 medical liquid passage 3 cap member 31 outercap 311 flange 312 fragile portion 313 flange 314 fanwise slit 32 innercap 33 annular ridge 4 closing member 5 sealing member 51 through hole52 flange 53 recess 54 annular rib 6 holding member 61 top wall 62 hole63 skirt 64 engagement pawl 65 cylinderical cover cap 651 fragileportion 652 longitudinal rib 7 gasket 8 plunger A temporary assembly oftip member etc.

1. A pre-filled syringe comprising a barrel made of glass and having ata distal end thereof a medical liquid discharge port formed into theshape of a vial mouth; a sealing member fitted in the medical liquiddischarge port of said barrel and having a through-hole in the axialdirection; a tip member including a skirt provided with an engagementpawl on a lower end inner wall thereof, a top wall, a needle mountingportion and a medical liquid deriving portion and forming a medicalliquid passage through said medical liquid deriving portion, said topwall and said needle mounting portion, and so mounted around saidsealing member on the medical liquid discharge port of said barrel as toslide along the outer wall of said medical liquid discharge port; a capmember mounted around said tip member; a closing member made integralwith said cap member and inserted into the medical liquid passage ofsaid tip member and the through-hole of said sealing member for closingsaid through-hole; and a holding member for mounting and fixing said tipmember on the medical liquid discharge port of said barrel, wherein saidtip member is mounted liquid-tightly on the medical liquid dischargeport by mounting said holding member around said tip member and slidingdownward along the skirt of said tip member to bring said engagementpawl of said tip member into engagement with said medical liquiddischarge port of said syringe.
 2. A pre-filled syringe as set forth inclaim 1, wherein said sealing member is a rubber plug having an annularrib on said top wall.
 3. A pre-filled syringe as set forth in claim 1 orclaim 2, wherein said tip member is provided at the skirt thereof withan axial slit and at the outer wall of a lower end portion thereof withretaining means for engaging with said holding member.
 4. A pre-filledsyringe as set forth in any of claims 1 and 3, wherein said needlemounting portion includes an inner side tip and outer side female jointmeans which are concentrically protruded on the outer side of said topwall of said tip member.
 5. A pre-filled syringe as set forth in any ofclaims 1 to 4, wherein said needle mounting portion is positionedeccentric from the axis of said tip member.
 6. A pre-filled syringe asset forth in any of claims 1 to 5, wherein said holding member isprovided at a lower end inner wall thereof with a skirt having anengagement pawl for engaging with the retaining means of said tipmember, and a top wall having a hole.
 7. A pre-filled syringe as setforth in any of claims 1 to 6, wherein said cap member includesconcentric inner and outer caps which are mounted around the tip of saidneedle mounting portion and said female joint means, respectively.
 8. Apre-filled syringe as set forth in claim 7, wherein said tip member ismounted liquid-tightly on the medical liquid discharge port by slidingsaid holding member which is temporarily assembled with the skirt upperend portion of the outer cap of said cap member downward along the outercap and the skirt of said tip member to bring the engagement pawl ofsaid tip member into engagement with the medical liquid discharge portof said barrel.
 9. A pre-filled syringe as set forth in claim 7, whereinsaid outer cap is provided with a flange at a skirt lower end portionand said flange removably held between the top wall of said holdingmember and the top wall of said tip member.
 10. A pre-filled syringe asset forth in claim 9, wherein said flange is provided with a fragileportion and said flange is broken at the fragile portion when said capmember is removed.
 11. A pre-filled syringe as set forth in claim 9,wherein said flange is formed thin and said flange is transformed andcomes off between the top wall of said holding member and the top wallof said tip member when said cap member is removed.
 12. A pre-filledsyringe as set forth in claim 11, wherein said flange is provided with afanwise slit.
 13. A pre-filled syringe as set forth in claim 7, whereinsaid outer cap is covered with a cylindrical cover cap which connectswith the top wall of said holding member through the fragile portion,and said cylindrical cover cap can be broken from the top wall of saidholding member.
 14. A pre-filled syringe as set forth in claim 12,wherein said cap member is removed with said cylindrical cover cap.